Clinical Trial Using an Engineered Peripheral Blood Graft for Haploidentical Transplantation

Central Venous Catheter:

The chemotherapy and some of the other drugs in this study will be given by vein through your
central venous catheter (CVC). A CVC is a sterile flexible tube and needle that will be
placed into a large vein while you are under local anesthesia. Blood samples will also be
drawn through your CVC. The CVC will remain in your body during treatment. Your doctor will
explain this procedure to you in more detail, and you will be required to sign a separate
consent form.

Chemotherapy and Stem Cell infusion:

You will receive 1 of 2 chemotherapy treatments (high-dose regimen or reduced-intensity
regimen) that will be chosen by your doctor. The treatment will be selected based on your age
and health. The high-dose regimen includes a higher dose of melphalan than the
reduced-intensity regimen. The doses of fludarabine and cyclophosphamide are the same.

Study Drug Administration:

On Day -7 (7 days before receiving the modified stem cell transplant), you will be admitted
to the hospital and given fluids by vein.

On Day -6, you will receive melphalan by vein over 30 minutes and fludarabine by vein over 1
hour. Fludarabine and melphalan are given to treat the cancer and lower the immune system in
order to lower the risk of rejecting the donor cells.

On Days -5 through -3, you will receive fludarabine by vein over 1 hour.

On Day -2, you will receive total body irradiation (TBI). TBI involves the delivery of high
doses of radiation designed to destroy cancer cells and/or lower the immune system in order
to lower the risk of the body rejecting the new stem cells.

On Day -1, you will "rest" (not receive chemotherapy).

On Day 0, you will receive the modified stem cell transplant by vein. The infusion will last
anywhere from about 30 minutes to several hours.

On Days +3 and +4, you will receive cyclophosphamide by vein over 3 hours. Cyclophosphamide
is given to lower the immune system in order to lower the risk of GVHD. You will also receive
mesna by vein over 30 minutes every 4 hours for a total of 10 mesna doses on Days +3 and +4.
Mesna is given to lower the risk of side effects to the bladder caused by cyclophosphamide.

Starting on Day +5, if you are one of the first 6 patients enrolled in the study, you will
receive tacrolimus to help lower the risk of GVHD. Tacrolimus will be given by vein as a
continuous infusion for about 2 weeks. After the 2 weeks of taking tacrolimus by vein, you
will take tacrolimus by mouth as a pill for at least 4 months.

Starting on Day +7, you will receive filgrastim as an injection under the skin 1 time a day,
until your blood cell levels are high enough. Filgrastim is designed to help with the growth
of a type of healthy white blood cells that fight infection.

Depending on the type of disease, your doctor may decide to give you rituximab by vein over
several hours on Days -13, -6, 1, and 8. Rituximab is given to help the body get rid of
abnormal white blood cells.

You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

Study Testing:

Before you are sent home from the hospital and/or clinic, you will receive additional written
instructions. These instructions will include how often you will come to the hospital/clinic,
which standard drugs you will take at home, and what side effects you may have and what to do
for them.

After finishing the chemotherapy and cell infusion, your follow-up care will be routine
standard of care follow-up that all patients receiving allogeneic stem cell transplantation
receive. At each visit, you will have a physical exam and will be checked for symptoms of
GVHD. You will be asked about any side effects you may have had. Blood (about 1 tablespoon)
will be drawn for routine tests.

Mouse protein antibodies are used in the T cell removal process. If your body becomes immune
to these proteins, you may develop antibodies against the mouse antibodies (called "human
anti-mouse antibodies" or HAMA). Blood samples drawn before the modified stem cell transplant
and about 3 months after the modified stem cell transplant will be used to compare against a
sample of your blood collected after the transplant is complete, to make sure you have not
developed an immune system reaction against these mouse protein antibodies. If you leave the
study before 3 months after the stem cell transplant, blood will be drawn to check for HAMA,
if possible.

If the doctor thinks it is needed, you will have a bone marrow aspiration to check the status
of the disease. To collect a bone marrow aspirate, an area of the hip or other site is numbed
with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Blood (up to about 4 tablespoons) will be drawn to test the genetic makeup and function of
the modified stem cells and to check the status of the disease about 1, 2, 3, 6, 9, and 12
months after the modified stem cell transplant.

Length of Treatment:

You will be on study for up to about 2 years. You may be taken off study early if the doctor
thinks it is in your best interest, if the disease gets worse or comes back and needs more
treatment, if intolerable side effects occur, if you are unable to follow study directions,
or if you choose to leave the study early.

If for any reason you want to leave the study early, you must talk to the study doctor. It
may be life-threatening to leave the study after you have started to receive the study drugs
but before you receive the stem cell transplant because your blood cell counts will be
dangerously low.

Inclusion Criteria:

1. Lack of an HLA matched related donor, lack of an immediately available 8/8 HLA matched
unrelated donor.

2. Patients must be >/= 18 and hematologic malignancy defined as one of the following:

3. Acute lymphocytic leukemia (ALL) in CR1 with high-risk features including adverse
cytogenetic such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; in second
or greater morphologic remission; persistent minimal residual disease;

4. Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease and persistent
detectable MRD, or with high-risk features defined as: greater than 1 cycle of
induction therapy required to achieve remission; preceding myelodysplastic syndrome
(MDS) or myeloproliferative disease; presence of FLT3 mutations or internal tandem
duplications, DNMT3a, TET2, MLL-PTD, ASXL1, PHF6; FAB M6 or M7 classification; adverse
cytogenetics including: -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q,
20q, 21q, 17, +8, complex [> 3 abnormalities];

5. Patients with AML must have less than 10% bone marrow blasts and < 100/mcL absolute
peripheral blood blast count;

6. MDS with IPSS intermediate-2 or higher, therapy-related MDS or CMML;

7. Aplastic anemia with ANC<1,000 and transfusion dependent after failed
immunosuppression therapy;

8. Chronic myeloid leukemia (CML) >/=1st chronic phase, after failed >/=2 lines of
tyrosine kinase inhibitors; patients who progressed to blast phase must be in
morphologic remission at transplant;

9. Relapsed Hodgkin's disease or non-Hodgkin's lymphoma (NHL);

10. Patients with chemo-sensitive chronic lymphocytic leukemia (CLL)/small lymphocytic
lymphoma (SLL) with persistent or recurrent disease after fludarabine-based regimens
with < 25% involvement by CLL/SLL cells;

11. Patients with poor prognosis multiple myeloma by cytogenetics (del13, del 17p, t(4,14)
or t(14;16) or hypodiploidy, with advanced disease (stage>/=2) and /or relapsed after
autologous stem cell transplant.

12. Zubrod performance status 0-1 or Karnofsky performance status > 70% . Patients > 50
years will have to have a Sorror Comorbidity Index
13. Available haploidentical donor willing and eligible to undergo a peripheral blood
collection;

14. LVEF> 40%;

15. Bilirubin adults. Conjugated (direct) bilirubin < 2x upper limit of normal;

16. Serum creatinine clearance >/= 50 ml/min (calculated with Cockcroft-Gault formula);

17. Diffusing capacity for carbon monoxide (DLCO) >/= 45% predicted corrected for
hemoglobin.

18. Patient or patient's legal representative must provide written informed consent.

Exclusion Criteria:

1. HIV positive; active hepatitis B or C.

2. Patients with active infections. The PI is the final arbiter of the eligibility.

3. Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis.

4. Uncontrolled CNS involvement by tumor cells within the past 2 months.

5. History of another primary malignancy that has not been in remission for at least 3
years. (The following are exempt from the 3-year limit: nonmelanoma skin cancer, fully
excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and
cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP
smear.)

6. Positive Beta HCG test in a woman with child bearing potential defined as not
post-menopausal for 12 months or no previous surgical sterilization.

7. Inability to comply with medical therapy or follow-up.